Transcript Warm Autoimmune Hemolytic Anemia

Warm Autoimmune
Hemolytic Anemia
Lisa Rose-Jones, MD
Monday, Aug 24th
Autoimmune Hemolytic
Anemia: Warm Agglutinins
• Due to IgG antibodies that react with
protein antigens on RBC surface @
body temperature
• Extravascular (red blood cells are
destroyed in the spleen and other
reticuloendothelial organs)
hemolysis
Hemolysis
Diagnosis:
• Typically find Hgb in range of 710 g/dL (Hct 21-30%)
• Hemolysis: Increased
Reticulocyte*/LDH/Indirect
Bilirubin; Decreased
Haptoglobin
*Some w/ acute hemolysis may have
reticulocytopenia from lag in marrow
responsiveness 2/2 hemolytic stress
Warm Hemolysis Dx
contd…
• Peripheral smear show
spherocytosis (appear
abnormally small and will lack
the central pallor)
Direct Coombs’ test
• Test for dignosis of warm AIHA
• Adherent proteins are washed free
from pt’s RBCs, mixed w/ antiserum
or monocolonal Abs against different
Immunoglobulins (IgG, C3d)= & if
present on RBC surface degree
agglutination quantitated by ELISA
Differential Diagnosis
~ Drug Induced:
Cephalosporins, PCN &
derivatives, NSAIDs, Quinidine
~Cold Agglutinins, (cold reacting
IgM antibodies). Acral cynaosis
Pathogenesis of RBC
destruction in AIHA:
Immunoadherence: RBC (target
cell) affixed to destructive cell
(phagocyte) through
immunoprotein molecule on
each cell
~ingestion may be partial, resulting in RBC
w/ reduced surface:vol ratio = spherocyte,
b/c reduced deformability many can’t cross
splenic sinuses slits=destroyed
Why Autoantibody
Production?
• B cell clones appear to be altered to
produce these antibodies at high
pathogenic titers
• Exacerbated by immune reaction of
microbial infection?, viral infections
(HIV, Mono)
• Rxn to blood transfusion or
transplant my initiate this process
Why?.......
• Higher incidence of
autoantibodies associated w/
Systemic Lupus
• 11% of patients’ w/ Chronic
Lymphocytic Leukemia (CLL),
likely b/c of again abnormal B
cells (neoplastic proliferation)
Treatment Goals:
** Reduce the amount of Antibody
being produced & reduce its effiency
in destroying RBCs
~Success ≠ Cure, typically still
evidence of persistent activity of
underlying process. Control degree
of anemia
Reduce Antibody
Response
1) Corticosteroids (1mg/kg
Prednisone), see response in 1-3
wks
2) Cytotoxic Agents: Azathioprine &
Cyclophosphamide, given if lack
response/inability tolerate #1.
Response seen ~ 1 month. Case
reports in resistant cases use of
Cyclosporine, Mycophenolate, and
anti-CD20 antibodies (Rituximab)
Reduce Antibody
Effectiveness
• Splenectomy (removing primary
site of destruction)
• IVIG: only occ effective (40%) in
tx of AIHA refractory to
conventional therapy w/
Prednisone & splenectomy
(reducing the interaction b/w
spleen macrophages & Ab
coated RBCs)
RBC Transfusions:
• Tested for alloantibodies*
(develops following pregnancy
or prior transfusions) &
autoantibodies
• Experience has indicated most
pts will tolerate serologically
incomplatible (atuoantibodies)
blood
THE END!!